[肾上腺髓质素对血管外膜成纤维细胞中血管紧张素II诱导的胶原蛋白合成的影响]

[Effects of adrenomedullin on angiotensin II-induced collagen synthesis in vascular adventitial fibroblasts].

作者信息

Liu Hai-chao, Ma Ye-xin, He Jun, Ke Jun

机构信息

Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

出版信息

Zhonghua Xin Xue Guan Bing Za Zhi. 2007 Sep;35(9):848-53.

PMID:18070482

Abstract

OBJECTIVE

To explore the effects of adrenomedullin (ADM) on Angiotensin II (AngII)-induced collagen synthesis in cultured rat vascular adventitial fibroblasts.

METHODS

Rat vascular adventitial fibroblasts were cultured in vitro. ADM produced and secreted from adventitia in the presence of AngII was detected by radioimmunoassay, type I, III collagen contents in adventitia fibroblasts were measured by ELISA and the expressions of TGFbeta1 and MMP-2 were determined by RT-PCR and Western blotting.

RESULTS

AngII significantly induced ADM secretion in adventitial fibroblasts in a dose-dependent manner. These effects could be reduced by 45%, 3% and 46%, through pre-treatment with Losartan, PD123319 or both, respectively for 30 min in culture medium. The AngII-induced type I, III collagen secretion in adventitial fibroblasts was significantly reduced by AMD in a dose-dependent manner, (P < 0.01) while ADM agonist ADM(22 - 52) significantly potentiated the effect of AngII; ADM also reduced AngII-induced expression of TGFbeta1 at mRNA and protein levels in a dose-dependent manner. AngII reduced the expression of MMP-2 at mRNA and protein levels in adventitial fibroblasts and these effects could be reversed by AMD (10(-8) mol/L).

CONCLUSION

AngII stimulated ADM secretion in adventitia fibroblasts, ADM in turn can inhibit AngII-induced type I, III collagen synthesis in adventitial fibroblasts probably by downregulating the TGFbeta1 expression and upregulating MMP-2 expression. ADM therefore served as an antifibrotic factor in vascular remodeling process.

摘要

目的

探讨肾上腺髓质素（ADM）对血管紧张素II（AngII）诱导的大鼠血管外膜成纤维细胞胶原合成的影响。

方法

体外培养大鼠血管外膜成纤维细胞。采用放射免疫分析法检测在AngII存在下外膜产生和分泌的ADM，用酶联免疫吸附测定法测量外膜成纤维细胞中I型、III型胶原含量，并用逆转录-聚合酶链反应（RT-PCR）和蛋白质印迹法检测转化生长因子β1（TGFbeta1）和基质金属蛋白酶-2（MMP-2）的表达。

结果

AngII以剂量依赖性方式显著诱导外膜成纤维细胞分泌ADM。在培养基中分别用氯沙坦、PD123319预处理30分钟或两者联合预处理，这些作用可分别降低45%、3%和46%。ADM以剂量依赖性方式显著降低AngII诱导的外膜成纤维细胞中I型、III型胶原分泌（P < 0.01），而ADM激动剂ADM(22 - 52)显著增强AngII的作用；ADM还以剂量依赖性方式降低AngII诱导的TGFbeta1在mRNA和蛋白质水平的表达。AngII降低外膜成纤维细胞中MMP-2在mRNA和蛋白质水平的表达，而ADM（10(-8) mol/L）可逆转这些作用。